scholarly journals Single Session of Fecal Microbiota Transplantation in Decompensated Cirrhosis: An open-label randomized control trial

2021 ◽  
Author(s):  
Akash Roy ◽  
Madhumita Premkumar ◽  
Anima Sharma ◽  
Nipun Verma ◽  
Surender Singh ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Fecal Microbiota Transplantation ◽  
Interleukin 1 ◽  
Fecal Microbiota ◽  
Prognostic Scores ◽  
Decompensated Cirrhosis ◽  
Single Session ◽  
Serious Adverse Events ◽  
Nasojejunal Tube ◽  
The Impact

Abstract Background: Modulation of gut dysbiosis with Fecal Microbiota Transplantation (FMT) is a novel modality and has shown promising results in decompensated cirrhosis (DC). We explored the impact of FMT on prognostic scores, complications, ammonia levels, inflammatory markers [(Interleukin -1 (IL-1) and 6 (IL-6)], and 180-day mortality in DC.Methods: Consecutive patients with DC (MELD12-21) were assigned to either FMT (FMT group) delivered as 30gm freshly prepared stool (from a related stool donor) homogenized in 100 ml of normal saline through a nasojejunal tube or standard of care therapy (SOC group). Outcomes were assessed on days 7, 28, 90, and 180.Results: Eighteen patients each with comparable baseline characteristics (88.8% males; mean age, 46.12±6.23 vs. 47.0±4.54; mean CTP, 9.5±0.71 vs. 9.6±0.80; mean MELD, 16.1±1.71 vs. 1.62±1.81) were allocated to FMT or SOC. Although significant differences were noted in the CTP score on day 7 (P=0.02) and day 90 (P=0.01), MELD and MELD-Na scores were similar at all time points. A non-significant reduction in ammonia levels was seen on day 7 and day 28 (P=0.21 and P=0.17; respectively). IL-1 (P=0.01) and IL 6 (P=0.005) levels reduced significantly on day 28. New-onset variceal bleed (P=0.70), breakthrough hepatic encephalopathy events (P=0.61) and 180-day survival (HR, 2.02; 95% CI, 0.37-11.05; P=0.41). were similar. Although transient gastrointestinal side-effects were common (56.2%), no serious adverse events were noted.Conclusion: Single session FMT in DC is safe and leads to selective improvement of CTP scores and systemic inflammatory markers but offers no survival benefit. (ClinicalTrials.gov number, NCT04842539)

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Oluwaseun Shogbesan ◽  
Dilli Ram Poudel ◽  
Samjeris Victor ◽  
Asad Jehangir ◽  
Opeyemi Fadahunsi ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
English Language ◽  
Fecal Microbiota Transplantation ◽  
Secondary Infection ◽  
Organ Transplant ◽  
Fecal Microbiota ◽  
Immunocompromised Patients ◽  
Serious Adverse Events ◽  
Fecal Microbiota Transplant ◽  
Immunosuppressant Medications

Background. Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown. Methods. We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated. Results. Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations. Conclusion. We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.

scholarly journals Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

2021 ◽  
Author(s):  
Ning-Jiun Jan ◽  
Noah Oakland ◽  
Pankaj Kumar ◽  
Girija Ramakrishnan ◽  
Brian W. Behm ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Fecal Microbiota Transplantation ◽  
Alpha Diversity ◽  
The United States ◽  
Fecal Microbiota ◽  
Peripheral Blood Mononuclear ◽  
Clostridioides Difficile ◽  
Rdna Sequencing ◽  
Clostridioides Difficile Infection ◽  
The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

scholarly journals Extended Screening Costs Associated With Selecting Donors for Fecal Microbiota Transplantation for Treatment of Metabolic Syndrome-Associated Diseases

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Laura J Craven ◽  
Seema Nair Parvathy ◽  
Justin Tat-Ko ◽  
Jeremy P Burton ◽  
Michael S Silverman
Keyword(s):  
Metabolic Syndrome ◽  
Fecal Microbiota Transplantation ◽  
The United States ◽  
Fecal Microbiota ◽  
Screening Programs ◽  
Central Processing ◽  
Donor Screening ◽  
Increased Risk ◽  
The Cost ◽  
The Impact

Abstract Background Knowledge of the impact of the gut microbiome on conditions other than Clostridium difficile infection has been rapidly increasing, and the potential usefulness of fecal microbiota transplantation (FMT) in these indications is being explored. The need to exclude donors with an increased risk of these diseases has left uncertainties regarding the cost and feasibility of donor screening. The aim of this study was to compare our experience to other donor-screening programs and report the costs associated with establishing a donor-screening program, for the treatment of metabolic syndrome-related conditions. Methods Forty-six potential donors (PDs) had their medical histories and physical examinations undertaken by a physician. Blood, stool, and urine were screened for 31 viral, bacterial, fungal, and protozoan agents in addition to biochemical characteristics. The price of advertising, doctor’s visits and diagnostic tests were calculated to determine the cost of finding a donor. Results Of the PDs screened, 5 of 46 passed the history, examination, blood, stool, and urine tests. The most common reasons for exclusion included a body mass index >25 or the detection of Blastocystis hominis, Dientamoeba fragilis, or Helicobacter pylori. Four of five eligible donors had subsequent travel or illness that contraindicated donation, so only 1 of 46 PDs was suitable. The total cost for finding a single suitable donor was $15190 US dollars. This screening was performed in Canada, and costs in the United States would be substantially higher. Conclusions New potential therapeutic uses for FMT have created a demand for stricter exclusion criteria for donors. This study illustrates that screening many individuals to find a donor and the subsequent associated costs may make central processing and shipment a more reasonable alternative.

scholarly journals 2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S896-S896
Author(s):  
Benoit Levast ◽  
Cécile Batailler ◽  
Cécile Pouderoux ◽  
Lilia Boucihna ◽  
Sébastien Lustig ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Joint Infection ◽  
Surrogate Marker ◽  
Generation Cephalosporin ◽  
Fecal Microbiota ◽  
Metagenomic Sequencing ◽  
Gut Dysbiosis ◽  
Prosthetic Joint ◽  
The Impact

Abstract Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

scholarly journals Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao-Ming Xu ◽  
Hong-Li Huang ◽  
Jing Xu ◽  
Jie He ◽  
Chong Zhao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Butyric Acid ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
16S Sequencing ◽  
Α Diversity ◽  
The Impact

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation

2019 ◽  
Vol 47 (4) ◽  
pp. 482-504 ◽  
Author(s):  
Alexander Khoruts ◽  
Diane E. Hoffmann ◽  
Francis B. Palumbo
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Drug Approval ◽  
Fecal Microbiota ◽  
Regulatory Decision ◽  
Regulatory Policies ◽  
Research And Innovation ◽  
Recurrent Clostridium Difficile Infection ◽  
Potential Impact ◽  
Approved Drugs ◽  
The Impact

In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug (IND) application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for drug approval and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation.

scholarly journals The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wai Ching Lam ◽  
Chen Zhao ◽  
Wen Juan Ma ◽  
Liang Yao
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Cohort Studies ◽  
Clinical Response ◽  
Clinical Remission ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Controlled Trials ◽  
Serious Adverse Events ◽  
Randomized Controlled

Background and Purpose. Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation. Methods. We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses. Key Results. A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P<0.001; I2=0%) and clinical response (OR, 2.75 [1.33, 5.67]; P=0.006; I2=49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P=0.37; I2=69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P=0.44; I2=0%). Conclusions and Inferences. Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.

scholarly journals Safety of fecal microbiota transplantation for Clostridioides difficile infection focusing on pathobionts and SARS-CoV-2

2021 ◽  
Vol 14 ◽  
pp. 175628482110096
Author(s):  
Devvrat Yadav ◽  
Sahil Khanna
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Success Rates ◽  
Serious Adverse Events ◽  
Additional Risk ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Clostridioides Difficile ◽  
Potential Pathogen ◽  
Clostridioides Difficile Infection

Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed.

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